Variably crosslinked tissue
AssigneeBiomedical Design, Inc.
InventorsJean-Marie Girardot, Marie-Nadia Girardot
Life of this patent
Estimating the term…
Abstract
Non-glutaraldehyde fixation of an organ or a prosthesis for implantation in a mammal is based upon carbodiimide treatment. A solution containing a sterilizing agent, such as EDC, in combination with a coupling enhancer, such as Sulfo-NHS, and a high concentration of a diamine cross linking agent is used. As a result, only minimal surface reduction occurs during fixation, and the resultant products show a dramatic increase in resistance to calcification.
Claims31
A method of making sterilized and partially cross linked biological tissue from fresh tissue, which method comprises the steps of:
- a) contacting fresh biological tissue with a cross linking solution containing a cross linking agent, from 1 to 5 mM of a coupling agent and a low concentration of a coupling enhancer to produce partially cross linked tissue, b) contacting the partially cross linked tissue with a blocking solution that comprises a monoamine blocking agent and a sterilizing agent;
- and c) then contacting said tissue with a final sterilizing solution that comprises a sterilizing agent and no blocking agent to produce the sterilized and partially cross linked biological tissue, which tissue has such a degree of cross linking that it resists enzymatic degradation to an extent that is statistically significantly less than fully cross linked tissue and statistically significantly greater than minimally cross linked tissue.
A method of making sterilized and partially cross linked biological tissue from fresh tissue which method comprises the steps of:
- a) contacting fresh biological tissue with a cross linking solution containing a cross linking agent, from 0.1 to 5 mM of a coupling agent and from 0.1 to 0.4 mM of a coupling enhancer to produce partially cross linked tissue, b) contacting the partially cross linked tissue with a blocking solution that comprises a monoamine blocking agent, a penetration enhancer and a sterilizing agent;
- and c) then contacting said tissue with a final sterilizing solution which final sterilizing solution comprises a sterilizing agent and no blocking agent to produce sterilized and partially cross linked biological tissue, which partially cross linked tissue when treated with 1 mg/ml of pronase for 24 hours at about 50° C. results in more than 50% but less than 80% tissue remaining
A method of making a sterilized and partially cross linked biological tissue from fresh tissue, which method comprises the steps of:
- a) contacting fresh biological tissue with a cross linking solution containing a cross linking agent, concentration of a carbodiimide coupling agent between about 1 and about 2.5 mM and a concentration of between 0.05 and 0.4 mM of a coupling enhancer to produce partially cross linked tissue, b) contacting the partially cross linked tissue with a blocking solution that comprises a monoamine blocking agent, and with a carbodiimide sterilizing agent in the presence of a penetration enhancer and c) then contacting said tissue with a final sterilizing solution which comprises a carbodiimide sterilizing agent and no blocking agent to produce sterilized and partially cross linked biological tissue, which tissue has a shrinkage temperature at least 4° C. above that of the fresh tissue and at least 6° C. below fully cross linked tissue.
Dependencies are inferred from the claim text.